Detailed structural insights into the p97-Npl4-Ufd1 interface

Rivka L. Isaacson, Valerie E. Pye, Peter Simpson, Hemmo H. Meyer, Xiaodong Zhang, Paul S. Freemont, Steve Matthews*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


The AAA ATPase, p97, achieves its versatility through binding to a wide range of cofactor proteins that adapt it to different cellular functions. The heterodimer UN (comprising Ufd1 and Npl4) is an adaptor complex that recruits p97 for numerous tasks, many of which involve the ubiquitin pathway. Insights into the structural specificity of p97 for its UN adaptor are currently negligible. Here, we present the solution structure of the Npl4 "ubiquitin-like" domain (UBD), which adopts a β-grasp fold with a 310 helical insert. Moreover we performed a chemical shift perturbation analysis of its binding surface with the p97 N domain. We assigned the backbone amides of the p97 N domain and probed both its reciprocal binding surface with Npl4 UBD and its interaction with the p97-binding region of Ufd1. NMR data recorded on a 400-kDa full-length UN-hexamer p97 complex reveals an identical mode of interaction. We calculated a structural model for the p97 N-Npl4 UBD complex, and a comparison with the p97-p47 adaptor complex reveals subtle differences in p97 adaptor recognition and specificity.

Original languageEnglish
Pages (from-to)21361-21369
Number of pages9
JournalJournal of Biological Chemistry
Issue number29
Publication statusPublished - 20 Jul 2007


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